1. Extracellular Vesicles From Mesenchymal Umbilical Cord Cells Exert Protection Against Oxidative Stress and Fibrosis in a Rat Model of Bronchopulmonary Dysplasia
- Author
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Bisaccia, Paola, Magarotto, Fabio, D’Agostino, Stefania, Dedja, Arben, Barbon, Silvia, Guidolin, Diego, Liboni, Cristina, Angioni, Roberta, De Lazzari, Giada, Caicci, Federico, Viola, Antonella, Jurga, Marcin, Kundrotas, Gabrielis, Stevens, Dimitri, Mancuso, Domenico, Gramegna, Elisabetta, Seitaj, Bruno, Kashyap, Rudra, De Vos, Beatrice, Macchi, Veronica, Baraldi, Eugenio, Porzionato, Andrea, De Caro, Raffaele, Muraca, Maurizio, and Pozzobon, Michela
- Abstract
Oxidative stress and fibrosis are important stress responses that characterize bronchopulmonary dysplasia (BPD), a disease for which only a therapy but not a cure has been developed. In this work, we investigated the effects of mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) on lung and brain compartment in an animal model of hyperoxia-induced BPD. Rat pups were intratracheally injected with MSC-EVs produced by human umbilical cord-derived MSC, following the Good Manufacturing Practice-grade (GMP-grade). After evaluating biodistribution of labelled MSC-EVs in rat pups left in normoxia and hyperoxia, oxidative stress and fibrosis investigation were performed. Oxidative stress protection by MSC-EVs treatment was proved both in lung and in brain. The lung epithelial compartment ameliorated glycosaminoglycan and surfactant protein expression in MSC-EVs-injected rat pups compared to untreated animals. Pups under hyperoxia exhibited a fibrotic phenotype in lungs shown by increased collagen deposition and also expression of profibrotic genes. Both parameters were reduced by treatment with MSC-EVs. We established an in vitro model of fibrosis and another of oxidative stress, and we proved that MSC-EVs suppressed the induction of αSMA, influencing collagen deposition and protecting from the oxidative stress. In conclusion, intratracheal administration of clinical-grade MSC-EVs protect from oxidative stress, improves pulmonary epithelial function, and counteracts the development of fibrosis. In the future, MSC-EVs could represent a new cure to prevent the development of BPD.Graphical AbstractClinical grade MSC-EVs were intratracheally injected in a rat model of broncopulmonary dysplasia. Fibrosis and oxidative stress have been analyzed in lung and brain without and with MSC-EVs.
- Published
- 2024
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